Zebrafish Mutants Calamity and Catastrophe Define Critical Pathways of Gene-nutrient Interactions in Developmental Copper Metabolism

Overview

Journal PLoS Genet

Specialty Genetics

Date 2008 Nov 15

PMID 19008952

Citations 28

Authors

Erik C Madsen

Jonathan D Gitlin

Affiliations

Soon will be listed here.

Abstract

Nutrient availability is an important environmental variable during development that has significant effects on the metabolism, health, and viability of an organism. To understand these interactions for the nutrient copper, we used a chemical genetic screen for zebrafish mutants sensitive to developmental copper deficiency. In this screen, we isolated two mutants that define subtleties of copper metabolism. The first contains a viable hypomorphic allele of atp7a and results in a loss of pigmentation when exposed to mild nutritional copper deficiency. This mutant displays incompletely penetrant skeletal defects affected by developmental copper availability. The second carries an inactivating mutation in the vacuolar ATPase that causes punctate melanocytes and embryonic lethality. This mutant, catastrophe, is sensitive to copper deprivation revealing overlap between ion metabolic pathways. Together, the two mutants illustrate the utility of chemical genetic screens in zebrafish to elucidate the interaction of nutrient availability and genetic polymorphisms in cellular metabolism.

Citing Articles

Inhibition of GPR68 kills glioblastoma in zebrafish xenograft models.

Neitzel L, Fuller D, Williams C, Hong C BMC Res Notes. 2024; 17(1):235.

PMID: 39180089 PMC: 11342492. DOI: 10.1186/s13104-024-06900-x.

Pigmentation and TYRP1 expression are mediated by zinc through the early secretory pathway-resident ZNT proteins.

Wagatsuma T, Suzuki E, Shiotsu M, Sogo A, Nishito Y, Ando H Commun Biol. 2023; 6(1):403.

PMID: 37072620 PMC: 10113262. DOI: 10.1038/s42003-023-04640-5.

Oral Elesclomol Treatment Alleviates Copper Deficiency in Animal Models.

Yuan S, Korolnek T, Kim B Front Cell Dev Biol. 2022; 10:856300.

PMID: 35433682 PMC: 9010564. DOI: 10.3389/fcell.2022.856300.

Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.

Hoareau M, El Kholti N, Debret R, Lambert E Int J Mol Sci. 2022; 23(4).

PMID: 35216218 PMC: 8875079. DOI: 10.3390/ijms23042102.

RAVE and Rabconnectin-3 Complexes as Signal Dependent Regulators of Organelle Acidification.

Jaskolka M, Winkley S, Kane P Front Cell Dev Biol. 2021; 9:698190.

PMID: 34249946 PMC: 8264551. DOI: 10.3389/fcell.2021.698190.

References

Malikova M, Shi J, Kandror K . V-type ATPase is involved in biogenesis of GLUT4 vesicles. Am J Physiol Endocrinol Metab. 2004; 287(3):E547-52. DOI: 10.1152/ajpendo.00571.2003. View

Dettmer J, Hong-Hermesdorf A, Stierhof Y, Schumacher K . Vacuolar H+-ATPase activity is required for endocytic and secretory trafficking in Arabidopsis. Plant Cell. 2006; 18(3):715-30. PMC: 1383645. DOI: 10.1105/tpc.105.037978. View

Kane P, Yamashiro C, Stevens T . Biochemical characterization of the yeast vacuolar H(+)-ATPase. J Biol Chem. 1989; 264(32):19236-44. View

Petris M, Strausak D, Mercer J . The Menkes copper transporter is required for the activation of tyrosinase. Hum Mol Genet. 2000; 9(19):2845-51. DOI: 10.1093/hmg/9.19.2845. View

Nguyen T, Novak E, Kermani M, Fluhr J, Peters L, Swank R . Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development. J Invest Dermatol. 2002; 119(5):1156-64. DOI: 10.1046/j.1523-1747.2002.19535.x. View

MENKES J, Alter M, Steigleder G, WEAKLEY D, Sung J . A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics. 1962; 29:764-79. View

Smith A, Lovering R, Futai M, Takeda J, Brown D, Karet F . Revised nomenclature for mammalian vacuolar-type H+ -ATPase subunit genes. Mol Cell. 2003; 12(4):801-3. DOI: 10.1016/s1097-2765(03)00397-6. View

MENKES J . Kinky hair disease: twenty five years later. Brain Dev. 1988; 10(2):77-9. DOI: 10.1016/s0387-7604(88)80074-3. View

Javidan Y, Schilling T . Development of cartilage and bone. Methods Cell Biol. 2004; 76:415-36. DOI: 10.1016/s0091-679x(04)76018-5. View

10.

Hillenmeyer M, Fung E, Wildenhain J, Pierce S, Hoon S, Lee W . The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science. 2008; 320(5874):362-5. PMC: 2794835. DOI: 10.1126/science.1150021. View

11.

Dmitriev O, Tsivkovskii R, Abildgaard F, Morgan C, Markley J, Lutsenko S . Solution structure of the N-domain of Wilson disease protein: distinct nucleotide-binding environment and effects of disease mutations. Proc Natl Acad Sci U S A. 2006; 103(14):5302-7. PMC: 1459350. DOI: 10.1073/pnas.0507416103. View

12.

Du S, Frenkel V, Kindschi G, Zohar Y . Visualizing normal and defective bone development in zebrafish embryos using the fluorescent chromophore calcein. Dev Biol. 2002; 238(2):239-46. DOI: 10.1006/dbio.2001.0390. View

13.

Taupenot L, Harper K, OConnor D . Role of H+-ATPase-mediated acidification in sorting and release of the regulated secretory protein chromogranin A: evidence for a vesiculogenic function. J Biol Chem. 2004; 280(5):3885-97. DOI: 10.1074/jbc.M408197200. View

14.

Kaler S, Holmes C, Goldstein D, Tang J, Godwin S, Donsante A . Neonatal diagnosis and treatment of Menkes disease. N Engl J Med. 2008; 358(6):605-14. PMC: 3477514. DOI: 10.1056/NEJMoa070613. View

15.

Huss M, Ingenhorst G, Konig S, Gassel M, Drose S, Zeeck A . Concanamycin A, the specific inhibitor of V-ATPases, binds to the V(o) subunit c. J Biol Chem. 2002; 277(43):40544-8. DOI: 10.1074/jbc.M207345200. View

16.

Gansner J, Mendelsohn B, Hultman K, Johnson S, Gitlin J . Essential role of lysyl oxidases in notochord development. Dev Biol. 2007; 307(2):202-13. PMC: 2467443. DOI: 10.1016/j.ydbio.2007.04.029. View

17.

Lin L, Horng J, Kunkel J, Hwang P . Proton pump-rich cell secretes acid in skin of zebrafish larvae. Am J Physiol Cell Physiol. 2005; 290(2):C371-8. DOI: 10.1152/ajpcell.00281.2005. View

18.

Johnson S, Africa D, Horne S, Postlethwait J . Half-tetrad analysis in zebrafish: mapping the ros mutation and the centromere of linkage group I. Genetics. 1995; 139(4):1727-35. PMC: 1206498. DOI: 10.1093/genetics/139.4.1727. View

19.

Czeizel A, Dudas I . Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992; 327(26):1832-5. DOI: 10.1056/NEJM199212243272602. View

20.

Tomashek J, Graham L, Hutchins M, Stevens T, Klionsky D . V1-situated stalk subunits of the yeast vacuolar proton-translocating ATPase. J Biol Chem. 1997; 272(42):26787-93. DOI: 10.1074/jbc.272.42.26787. View